PPH 407 Biopharmaceutics & Pharmacokinetics Lecture 1

PPH 407 BIOPHARMACEUTICS & PHARMACOKINETICS LECTURE 1 PROF. GIHAN SALAH MOHAMED LABIB  COURSE DESCRIPTION BIOPHARMACEUTICS The course addresses biopharmaceutics and pharmacokinetics disciplines useful to improve...

PPH 407 BIOPHARMACEUTICS & PHARMACOKINETICS LECTURE 1 PROF. GIHAN SALAH MOHAMED LABIB  COURSE DESCRIPTION BIOPHARMACEUTICS The course addresses biopharmaceutics and pharmacokinetics disciplines useful to improve the outcome of drug therapies, assist drug product development, and establish pharmacokinetics-pharmacodynamics models and in vitro- in vivo correlations. An emphasis is made on the pharmacokinetics of drugs administered by IV route, compartmental models, and renal and hepatic clearance. The course addresses how non compartmental pharmacokinetics can be used in computing the pharmacokinetic parameters of a drug from the time course of measured drug concentrations. Bioavailability and bioequivalence are introduced with discussion of their implication in the Egyptian pharmaceutical industry. This course further aims to provide students with an understanding of the relation between the physicochemical properties of the drug and its fate in the body. Thus, this course explores the principles of biopharmaceutics and strategies for enhancing drug delivery and bioavailability. Integration of 2 knowledge gained from other courses is emphasized to design and assure the quality of drug BIOPHARMACEUTICS About the course Credit hours: 4 hours Lectures: 2 hours Tutorial/ Practical: 2 hours Course team Professor/ Gihan Salah Labib Dr. / Shaimaa Osama Demonstrators/ Sylvia Tharwat, Joely, Salma, Diana, 3 Marram Yasser BIOPHARMACEUTICS Office hours of Professor Gihan Labib Tuesday : from 9:15 to10:15 a.m. At 2nd floor B09: 3040 4 BIOPHARMACEUTICS Course assessment: This course is 4 credits (100 Marks) 30% Midterm (30 marks) week 7 & week 12 30% Course work (30 Marks) Practical, Assignments& Interactive activities, Quizzes 40 % Final Exam (40 Marks) BIOPHARMACEUTICS Intended Learning Outcomes “ILO’s” Knowledge Skills Intellectual Skills Professional Skills General Skills BIOPHARMACEUTICS INTENDED LEARNING OUTCOMES “ILO’S” After lectures the student should be able to: Recognize factors affecting dosage forms performance. Recognize the importance of those factors when designing dosage forms according to the route of administration Evaluate factors affecting dosage forms performance & implement this knowledge to design an effective dosage form and predict dosage requirements. Identify, suggest solutions for bioavailability problems BIOPHARMACEUTICS INTENDED LEARNING OUTCOMES “ILO’S” Interpret and assess the pharmacokinetics data following drug administration Show all influencing factors, once involved in the domain of dosage form design Interpret experimental results, this will help in the domain of research, bioequivalence studies, drug-products industry  BIOPHARMACEUTICS DEFINITION The study of HOW the physicochemical properties of the drug, dosage forms, and route of administration affect the bioavailability (Rate (Tmax) & Extent (Cmax) of drug absorption) Goal of Biopharmaceutics Prepare a dosage form of good bioavailability BIOPHARMACEUTICS 10 ADME are known as Pharmacokinetics BIOPHARMACEUTICS ADME ABSORPTION: Transfer of drug from site of administration to the blood DISTRIBUTION: A dynamic equilibrium exists between the concentration of the drug in the blood plasma and the drug at its site(s) of action METABOLISM: Drug undergoing cleavage by enzymes or by biochemical transformation to be eliminated ELIMINATION: Removal of the drug from systemic circulation by excretion either unchanged or after metabolism 11 BIOPHARMACEUTICS Biopharmaceutics is concerned with the first stage – getting the drug from its route of administration into the blood stream or systemic circulation 12 BIOPHARMACEUTICS Concept of Bioavailability Bioavailability definition: The percentage of an administered dose of a particular drug that reaches the systemic circulation intact is known as the bioavailability The amount of an administered dose of the drug that reach the systemic circulation in the unchanged form is known as the bioavailable dose Example: I.V. injection has 100% bioavailability Any other route of administration, will differ according to the amount of drug administered that reach the circulation unchanged 13 Bioavailability is defined in the FDA's regulations as ‘the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action ’. BIOPHARMACEUTICS Many factors Influence the rate and extent of drug absorption: Food (Food-Drug interaction) Co- administration of other drugs (Drug-drug interaction) Age and diseased state of the patient Site of absorption Physicochemical properties of the drug Type of dosage form, Formulation, Method of manufacturing and dosing regimen BIOPHARMACEUTICS A given drug may exhibit differences in bioavailability: Same dosage form, but different route (Oral - IM solution) Same route, but different dosage form (Oral Tab - Solution) Same dosage form, Same route - different formulations BIOPHARMACEUTICS Variability in the bioavailability exhibited by a given drug from different formulations of the same type of dosage form, or from different types of dosage forms, or by different routes of administration, can cause the plasma concentration of the drug to be too high, and therefore cause side-effects, or too low, and therefore the drug will be ineffective. 17 18 PRESENTATION TITLE BIOPHARMACEUTICS BIOPHARMACEUTICS Poor biopharmaceutical properties may result in: Poor and variable bioavailability Difficulties in toxicological evaluation Difficulties with bioequivalence of formulations Multiple daily dosing The requirement for a non-conventional delivery system Long and costly development times High cost of products. 19 POSSIBLE ROUTES FOR DRUG ADMINISTRATION ORAL ROUTE Mucosal or Oral Transmucosal Nasal Buccal, Sublingual Routes Rectal, Vaginal, Ocular Non- Transdermal oral (Percutaneous) Parenteral routes ORAL ROUTE ORAL ROUTE OF ADMINISTRATION 21  ANATOMY OF THE GIT GIT starts from the mouth and ends at the anus ▪Stomach: Acidic pH (1-3), 1.5 L capacity (~50mL gastric fluid in fasting condition) Smooth S.A. Lined with mucus The main function : Storage, mixing and digestion The stomach delivers the digested food to the duodenum in a controlled manner ▪Small intestine: pH: 5-7, Duodenum (0.3m), Jejunum (2m), Ileum (3m). Villi & microvilli & high blood flow Large luminal S.A. 200 m2 The main function : Complete digestion , Main site of absorption First pass metabolism Salfasalazine ▪Large intestine: pH: 7-8 Large internal diameter Lacks villi Absorption of water, electrolytes-storage, compaction & elimination of fecal material. The colon is permanently colonized by bacteria capable of several metabolic reactions, e.g. hydrolysis of fatty acid esters. Colon-targeting The intestinal cells : Mucus and Enzymes: hydrolases and proteases Brunner’s glands in the duodenum : Bicarbonate to neutralize the acid emptied from the stomach Pancreatic secretions: Sodium bicarbonate and Enzymes; Proteases, lipase and amylase Liver: Bile secretion that promotes fat absorption by aiding its emulsification and micellar solubilization  Drug absorption ORAL ROUTE ▪ Once a drug is in solution, it has the potential to be absorbed ▪ Drug absorption: the penetration of the drug across the intestinal membrane and its appearance unchanged in the blood  Structure of the GIT membrane - Lipid-bilayer ORAL ROUTE - Protein, transporter proteins - Water-filled channels between cells(~ 7-10Å)  Structure of the GIT membrane - Lipid-bilayer - Protein, transporter proteins - Lipoproteins, glycoproteins and polysaccharides  There are two main mechanisms: 1. Transcelluar Transport 2. Paracellular Transport MECHANISMS OF DRUG ABSORPTION THROUGH THE GIT 1. Transcellular pathway: (across cells) 1.1. Passive diffusion (The main mechanism) 1.2. Carrier-mediated transport 1.2.1. Active transport 1.2.2. Facilitated diffusion 1.3. Pinocytosis or endocytosis 2. Paracellular pathway: ( between cells) 28 ORAL ROUTE  1.1. PASSIVE TRANSPORT 1. Transcellular pathway: ORAL ROUTE 1.1. Passive diffusion 1.2. Carrier-mediated transport 1.2.1. Active transport 1.2.2. Facilitated diffusion 1.3. Pinocytosis The concentration gradient is the driving force Small lipophilic molecules The membrane acts as simple barrier to diffusion As a semi permeable membrane allowing passage of some molecules and prevent others according to the properties of the drug  1.1. PASSIVE TRANSPORT The transport follows Fick’s first law of diffusion: ORAL ROUTE dC/dt α (C GIT- Cblood) dC/dt = K (CGIT- Cblood) dC/dt= Rate of drug diffusion at the site of absorption K= Permeability Constant = AD/h A= S.A. of the membrane D= Diffusion coefficient of the drug (Viscosity, P.C, size) Cblood